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1.
J Neurooncol ; 169(2): 247-256, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38837018

RESUMEN

OBJECTIVE: Survivors of pediatric brain tumors (SPBT) are at risk for social deficits, fewer friendships, and poor peer relations. SPBT also experience reduced brain connectivity via microstructural disruptions to white matter from neurological insults. Research with other populations implicates white matter connectivity as a key contributor to poor social functioning. This case-controlled diffusion-weighted imaging study evaluated structural connectivity in SPBT and typically developing controls (TDC) and associations between metrics of connectivity and social functioning. METHODS: Diffusion weighted-imaging results from 19 SPBT and 19 TDC were analyzed using probabilistic white matter tractography. Survivors were at least 5 years post-diagnosis and 2 years off treatment. Graph theory statistics measured group differences across several connectivity metrics, including average strength, global efficiency, assortativity, clustering coefficient, modularity, and betweenness centrality. Analyses also evaluated the effects of neurological risk on connectivity among SPBT. Correlational analyses evaluated associations between connectivity and indices of social behavior. RESULTS: SPBT demonstrated reduced global connectivity compared to TDC. Several medical factors (e.g., chemotherapy, recurrence, multimodal therapy) were related to decreased connectivity across metrics of integration (e.g., average strength, global efficiency) in SPBT. Connectivity metrics were related to peer relationship quality and social challenges in the SPBT group and to social challenges in the total sample. CONCLUSIONS: Microstructural white matter connectivity is diminished in SPBT and related to neurological risk and peer relationship quality. Additional neuroimaging research is needed to evaluate associations between brain connectivity metrics and social functioning in SPBT.


Asunto(s)
Neoplasias Encefálicas , Supervivientes de Cáncer , Sustancia Blanca , Humanos , Neoplasias Encefálicas/psicología , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/patología , Femenino , Masculino , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/patología , Niño , Adolescente , Supervivientes de Cáncer/psicología , Estudios de Casos y Controles , Imagen de Difusión por Resonancia Magnética , Imagen de Difusión Tensora , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Conducta Social , Adulto Joven , Vías Nerviosas/diagnóstico por imagen , Vías Nerviosas/patología
2.
J Clin Oncol ; 42(4): 441-451, 2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-37978951

RESUMEN

PURPOSE: The PNOC001 phase II single-arm trial sought to estimate progression-free survival (PFS) associated with everolimus therapy for progressive/recurrent pediatric low-grade glioma (pLGG) on the basis of phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway activation as measured by phosphorylated-ribosomal protein S6 and to identify prognostic and predictive biomarkers. PATIENTS AND METHODS: Patients, age 3-21 years, with progressive/recurrent pLGG received everolimus orally, 5 mg/m2 once daily. Frequency of driver gene alterations was compared among independent pLGG cohorts of newly diagnosed and progressive/recurrent patients. PFS at 6 months (primary end point) and median PFS (secondary end point) were estimated for association with everolimus therapy. RESULTS: Between 2012 and 2019, 65 subjects with progressive/recurrent pLGG (median age, 9.6 years; range, 3.0-19.9; 46% female) were enrolled, with a median follow-up of 57.5 months. The 6-month PFS was 67.4% (95% CI, 60.0 to 80.0) and median PFS was 11.1 months (95% CI, 7.6 to 19.8). Hypertriglyceridemia was the most common grade ≥3 adverse event. PI3K/AKT/mTOR pathway activation did not correlate with clinical outcomes (6-month PFS, active 68.4% v nonactive 63.3%; median PFS, active 11.2 months v nonactive 11.1 months; P = .80). Rare/novel KIAA1549::BRAF fusion breakpoints were most frequent in supratentorial midline pilocytic astrocytomas, in patients with progressive/recurrent disease, and correlated with poor clinical outcomes (median PFS, rare/novel KIAA1549::BRAF fusion breakpoints 6.1 months v common KIAA1549::BRAF fusion breakpoints 16.7 months; P < .05). Multivariate analysis confirmed their independent risk factor status for disease progression in PNOC001 and other, independent cohorts. Additionally, rare pathogenic germline variants in homologous recombination genes were identified in 6.8% of PNOC001 patients. CONCLUSION: Everolimus is a well-tolerated therapy for progressive/recurrent pLGGs. Rare/novel KIAA1549::BRAF fusion breakpoints may define biomarkers for progressive disease and should be assessed in future clinical trials.


Asunto(s)
Everolimus , Glioma , Humanos , Niño , Femenino , Preescolar , Adolescente , Adulto Joven , Adulto , Masculino , Everolimus/efectos adversos , Proteínas Proto-Oncogénicas B-raf/genética , Proteínas Proto-Oncogénicas c-akt , Fosfatidilinositol 3-Quinasas , Glioma/tratamiento farmacológico , Glioma/genética , Serina-Treonina Quinasas TOR/metabolismo , Serina-Treonina Quinasas TOR/uso terapéutico , Biomarcadores
3.
J Pediatr Hematol Oncol ; 45(6): 333-338, 2023 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-37314947

RESUMEN

Young children undergoing treatment with intensive chemotherapy for high-grade central nervous system (CNS) tumors are at risk for malnutrition, yet no guidelines exist for the placement of enteral tubes. Prior studies evaluated the impact of proactive gastrostomy tube (GT) placement with a narrow scope of outcomes, such as weight. To examine the impact of proactive GT on comprehensive treatment outcomes, we performed a single-center, retrospective study of children younger than 60 months of age with high-grade CNS tumors treated per CCG99703 or ACNS0334 between 2015 and 2022. Of 26 patients included, 9 (35%) underwent proactive GT, 8 (30%) had rescue GT, and 9 (35%) had a nasogastric tube (NGT). Clinically significant weight loss occurred in 47% of patients with NGT during induction compared with 22% with proactive GT ( P = 0.274); however, between cohorts, there was no significant difference in antibiotic or parenteral nutrition utilization, weight loss at therapy completion, and duration of hospitalization. Therefore, proactive GT placement was modestly effective at preventing significant weight loss during induction, however, there was no clear benefit for hospitalization duration, antibiotic, or parental nutrition requirements compared with NGT. We recommend an individualized approach to GT placement for young children with CNS malignancies undergoing intensive chemotherapy.


Asunto(s)
Neoplasias del Sistema Nervioso Central , Gastrostomía , Humanos , Niño , Preescolar , Nutrición Enteral , Estudios Retrospectivos , Resultado del Tratamiento , Neoplasias del Sistema Nervioso Central/terapia
4.
Cancers (Basel) ; 15(9)2023 May 05.
Artículo en Inglés | MEDLINE | ID: mdl-37174087

RESUMEN

Limited therapies exist for neurofibromatosis type 1 (NF1)-associated plexiform neurofibroma (PN). For this reason, the activity of vinblastine (VBL) and methotrexate (MTX) was evaluated in children and young adults with NF1 and PN. Patients ≤ 25 years of age with progressive and/or inoperable NF1-PN received VBL 6 mg/m2 and MTX 30 mg/m2 weekly for 26 weeks, followed by every 2 weeks for 26 weeks. Objective response rate was the primary endpoint. Of 25 participants enrolled, 23 were evaluable. The median age of participants was 6.6 years (range 0.3-20.7). The most frequent toxicities were neutropenia and elevation of transaminases. On two-dimensional (2D) imaging, 20 participants (87%) had stable tumor, with a median time to progression of 41.5 months (95% confidence interval 16.9, 64.9). Two of eight participants (25%) with airway involvement demonstrated functional improvements including decreased positive pressure requirements and apnea-hypopnea index. A post hoc three-dimensional (3D) analysis of PN volumes was completed on 15 participants with amenable imaging; 7 participants (46%) had progressive disease on or by the end of therapy. VBL/MTX was well-tolerated but did not result in objective volumetric response. Furthermore, 3D volumetric analysis highlighted the lack of sensitivity of 2D imaging for PN response evaluation.

5.
Clin Cancer Res ; 29(23): 4770-4783, 2023 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-37126021

RESUMEN

PURPOSE: Checkpoint inhibitors have limited efficacy for children with unselected solid and brain tumors. We report the first prospective pediatric trial (NCT02992964) using nivolumab exclusively for refractory nonhematologic cancers harboring tumor mutation burden (TMB) ≥5 mutations/megabase (mut/Mb) and/or mismatch repair deficiency (MMRD). PATIENTS AND METHODS: Twenty patients were screened, and 10 were ultimately included in the response cohort of whom nine had TMB >10 mut/Mb (three initially eligible based on MMRD) and one patient had TMB between 5 and 10 mut/Mb. RESULTS: Delayed immune responses contributed to best overall response of 50%, improving on initial objective responses (20%) and leading to 2-year overall survival (OS) of 50% [95% confidence interval (CI), 27-93]. Four children, including three with refractory malignant gliomas are in complete remission at a median follow-up of 37 months (range, 32.4-60), culminating in 2-year OS of 43% (95% CI, 18.2-100). Biomarker analyses confirmed benefit in children with germline MMRD, microsatellite instability, higher activated and lower regulatory circulating T cells. Stochastic mutation accumulation driven by underlying germline MMRD impacted the tumor microenvironment, contributing to delayed responses. No benefit was observed in the single patient with an MMR-proficient tumor and TMB 7.4 mut/Mb. CONCLUSIONS: Nivolumab resulted in durable responses and prolonged survival for the first time in a pediatric trial of refractory hypermutated cancers including malignant gliomas. Novel biomarkers identified here need to be translated rapidly to clinical care to identify children who can benefit from checkpoint inhibitors, including upfront management of cancer. See related commentary by Mardis, p. 4701.


Asunto(s)
Neoplasias Encefálicas , Glioma , Humanos , Niño , Nivolumab/uso terapéutico , Estudios Prospectivos , Mutación , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patología , Glioma/tratamiento farmacológico , Glioma/genética , Glioma/patología , Biomarcadores de Tumor/genética , Reparación de la Incompatibilidad de ADN/genética , Microambiente Tumoral
7.
J Pediatr Hematol Oncol ; 44(4): e859-e865, 2022 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-35235547

RESUMEN

Children with cancer and those undergoing hematopoietic stem cell transplantation frequently require anesthesia for imaging as well as diagnostic and therapeutic procedures from diagnosis through follow-up. Due to their underlying disease and side effects of chemotherapy and radiation, they are at risk for complications during this time, yet no published guideline exists for preanesthesia preparation. A comprehensive literature review served as the basis for discussions among our multidisciplinary panel of oncologists, anesthesiologists, nurse practitioners, clinical pharmacists, pediatric psychologists, surgeons and child life specialists at the Children's Hospital of Philadelphia. Due to limited literature available, this panel created an expert consensus guideline addressing anesthesia preparation for this population.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Neoplasias , Anestesia General/efectos adversos , Niño , Consenso , Diagnóstico por Imagen , Humanos , Neoplasias/terapia
8.
Neuro Oncol ; 24(9): 1598-1608, 2022 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-35148393

RESUMEN

BACKGROUND: Cross-sectional tumor measures are traditional clinical trial endpoints; however volumetric measures may better assess tumor growth. We determined the correlation and compared the prognostic impact of cross-sectional and volumetric measures of progressive disease (PD) among patients with DIPG. METHODS: Imaging and clinical data were abstracted from the International DIPG Registry. Tumor volume and cross-sectional product (CP) were measured with mint Lesion™ software using manual contouring. Correlation between CP and volume (segmented and mathematical [ellipsoid] model) thresholds of PD were assessed by linear regression. Landmark analyses determined differences in survival (via log-rank) between patients classified as PD versus non-PD by CP and volumetric measurements at 1, 3, 5, 7, and 9 months postradiotherapy (RT). Hazard ratios (HR) for survival after these time points were calculated by Cox regression. RESULTS: A total of 312 MRIs (46 patients) were analyzed. Comparing change from the previous smallest measure, CP increase of 25% (PD) correlated with a segmented volume increase of 30% (R2 = 0.710), rather than 40% (spherical model extrapolation). CP-determined PD predicted survival at 1 month post-RT (HR = 2.77), but not other time points. Segmented volumetric-determined PD (40% threshold) predicted survival at all imaging timepoints (HRs = 2.57, 2.62, 3.35, 2.71, 16.29), and 30% volumetric PD threshold predicted survival at 1, 3, 5, and 9 month timepoints (HRs = 2.57, 2.62, 4.65, 5.54). Compared to ellipsoid volume, segmented volume demonstrated superior survival associations. CONCLUSIONS: Segmented volumetric assessments of PD correlated better with survival than CP or ellipsoid volume at most time points. Semiautomated tumor volume likely represents a more accurate, prognostically-relevant measure of disease burden in DIPG.


Asunto(s)
Astrocitoma , Neoplasias del Tronco Encefálico , Glioma Pontino Intrínseco Difuso , Glioma , Humanos , Neoplasias del Tronco Encefálico/diagnóstico por imagen , Neoplasias del Tronco Encefálico/tratamiento farmacológico , Neoplasias del Tronco Encefálico/radioterapia , Estudios Transversales , Glioma/patología , Sistema de Registros
9.
Neuro Oncol ; 24(1): 141-152, 2022 01 05.
Artículo en Inglés | MEDLINE | ID: mdl-34114629

RESUMEN

BACKGROUND: Diffuse intrinsic pontine gliomas (DIPG) generally occur in young school-age children, although can occur in adolescents and young adults. The purpose of this study was to describe clinical, radiological, pathologic, and molecular characteristics in patients ≥10 years of age with DIPG enrolled in the International DIPG Registry (IDIPGR). METHODS: Patients ≥10 years of age at diagnosis enrolled in the IDIPGR with imaging confirmed DIPG diagnosis were included. The primary outcome was overall survival (OS) categorized as long-term survivors (LTS) (≥24 months) or short-term survivors (STS) (<24 months). RESULTS: Among 1010 patients, 208 (21%) were ≥10 years of age at diagnosis; 152 were eligible with a median age of 12 years (range 10-26.8). Median OS was 13 (2-82) months. The 1-, 3-, and 5-year OS was 59.2%, 5.3%, and 3.3%, respectively. The 18/152 (11.8%) LTS were more likely to be older (P < .01) and present with longer symptom duration (P < .01). Biopsy and/or autopsy were performed in 50 (33%) patients; 77%, 61%, 33%, and 6% of patients tested had H3K27M (H3F3A or HIST1H3B), TP53, ATRX, and ACVR1 mutations/genome alterations, respectively. Two of 18 patients with IDH1 testing were IDH1-mutant and 1 was a LTS. The presence or absence of H3 alterations did not affect survival. CONCLUSION: Patients ≥10 years old with DIPG have a median survival of 13 months. LTS present with longer symptom duration and are likely to be older at presentation compared to STS. ATRX mutation rates were higher in this population than the general DIPG population.


Asunto(s)
Astrocitoma , Neoplasias del Tronco Encefálico , Glioma Pontino Intrínseco Difuso , Glioma , Adolescente , Adulto , Neoplasias del Tronco Encefálico/genética , Niño , Glioma/genética , Humanos , Sistema de Registros , Adulto Joven
10.
Neuro Oncol ; 24(5): 821-833, 2022 05 04.
Artículo en Inglés | MEDLINE | ID: mdl-34668975

RESUMEN

BACKGROUND: Diffuse intrinsic pontine glioma (DIPG) remains a clinico-radiologic diagnosis without routine tissue acquisition. Reliable imaging distinction between DIPG and other pontine tumors with potentially more favorable prognoses and treatment considerations is essential. METHODS: Cases submitted to the International DIPG registry (IDIPGR) with histopathologic and/or radiologic data were analyzed. Central imaging review was performed on diagnostic brain MRIs (if available) by two neuro-radiologists. Imaging features suggestive of alternative diagnoses included nonpontine origin, <50% pontine involvement, focally exophytic morphology, sharply defined margins, and/or marked diffusion restriction throughout. RESULTS: Among 286 patients with pathology from biopsy and/or autopsy, 23 (8%) had histologic diagnoses inconsistent with DIPG, most commonly nondiffuse low-grade gliomas and embryonal tumors. Among 569 patients with centrally-reviewed diagnostic MRIs, 40 (7%) were classified as non-DIPG, alternative diagnosis suspected. The combined analysis included 151 patients with both histopathology and centrally-reviewed MRI. Of 77 patients with imaging classified as characteristic of DIPG, 76 (99%) had histopathologic diagnoses consistent with DIPG (infiltrating grade II-IV gliomas). Of 57 patients classified as likely DIPG with some unusual imaging features, 55 (96%) had histopathologic diagnoses consistent with DIPG. Of 17 patients with imaging features suggestive of an alternative diagnosis, eight (47%) had histopathologic diagnoses inconsistent with DIPG (remaining patients were excluded due to nonpontine tumor origin). Association between central neuro-imaging review impression and histopathology was significant (p < 0.001), and central neuro-imaging impression was prognostic of overall survival. CONCLUSIONS: The accuracy and important role of central neuro-imaging review in confirming the diagnosis of DIPG is demonstrated.


Asunto(s)
Astrocitoma , Neoplasias del Tronco Encefálico , Glioma , Humanos , Neoplasias del Tronco Encefálico/patología , Glioma/diagnóstico por imagen , Glioma/patología , Sistema de Registros
11.
J Int Neuropsychol Soc ; 28(9): 937-946, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-34605383

RESUMEN

OBJECTIVE: The neural mechanisms contributing to the social problems of pediatric brain tumor survivors (PBTS) are unknown. Face processing is important to social communication, social behavior, and peer acceptance. Research with other populations with social difficulties, namely autism spectrum disorder, suggests atypical brain activation in areas important for face processing. This case-controlled functional magnetic resonance imaging (fMRI) study compared brain activation during face processing in PBTS and typically developing (TD) youth. METHODS: Participants included 36 age-, gender-, and IQ-matched youth (N = 18 per group). PBTS were at least 5 years from diagnosis and 2 years from the completion of tumor therapy. fMRI data were acquired during a face identity task and a control condition. Groups were compared on activation magnitude within the fusiform gyrus for the faces condition compared to the control condition. Correlational analyses evaluated associations between neuroimaging metrics and indices of social behavior for PBTS participants. RESULTS: Both groups demonstrated face-specific activation within the social brain for the faces condition compared to the control condition. PBTS showed significantly decreased activation for faces in the medial portions of the fusiform gyrus bilaterally compared to TD youth, ps ≤ .004. Higher peak activity in the left fusiform gyrus was associated with better socialization (r = .53, p < .05). CONCLUSIONS: This study offers initial evidence of atypical activation in a key face processing area in PBTS. Such atypical activation may underlie some of the social difficulties of PBTS. Social cognitive neuroscience methodologies may elucidate the neurobiological bases for PBTS social behavior.


Asunto(s)
Trastorno del Espectro Autista , Neoplasias Encefálicas , Reconocimiento Facial , Adolescente , Encéfalo , Mapeo Encefálico , Neoplasias Encefálicas/diagnóstico por imagen , Niño , Humanos , Imagen por Resonancia Magnética/métodos , Sobrevivientes , Lóbulo Temporal/diagnóstico por imagen
12.
Front Oncol ; 11: 744739, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34540703

RESUMEN

PURPOSE: Medulloblastoma is one of the most common malignant brain tumors in children. To date, the treatment of average-risk (non-metastatic, completely resected) medulloblastoma includes craniospinal radiation therapy and adjuvant chemotherapy. Modern treatment modalities and now risk stratification of subgroups have extended the survival of these patients, exposing the long-term morbidities associated with radiation therapy. Prior to advances in molecular subgrouping, we sought to reduce the late effects of radiation in patients with average-risk medulloblastoma. METHODS: We performed a single-arm, multi-institution study, reducing the dose of craniospinal irradiation by 25% to 18 Gray (Gy) with the goal of maintaining the therapeutic efficacy as described in CCG 9892 with maintenance chemotherapy. RESULTS: Twenty-eight (28) patients aged 3-30 years were enrolled across three institutions between April 2001 and December 2010. Median age at enrollment was 9 years with a median follow-up time of 11.7 years. The 3-year relapse-free (RFS) and overall survival (OS) were 79% (95% confidence interval [CI] 58% to 90%) and 93% (95% CI 74% to 98%), respectively. The 5-year RFS and OS were 71% (95% CI 50% to 85%) and 86% (95% CI 66% to 94%), respectively. Toxicities were similar to those seen in other studies; there were no grade 5 toxicities. CONCLUSIONS: Given the known neurocognitive adverse effects associated with cranial radiation therapy, studies to evaluate the feasibility of dose reduction are needed. In this study, we demonstrate that select patients with average-risk medulloblastoma may benefit from a reduced craniospinal radiation dose of 18 Gy without impacting relapse-free or overall survival. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00031590.

13.
Pediatr Blood Cancer ; 68(11): e29282, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34383370

RESUMEN

BACKGROUND: Sorafenib,an orally bioavailable, multitarget tyrosine kinase inhibitor, and irinotecan, a topoisomerase I inhibitor, have demonstrated activity in pediatric and adult malignancies. We evaluated the toxicity, pharmacokinetic (PK), and pharmacogenomic (PGX) profile of sorafenib with irinotecan in children with relapsed or refractory solid tumors and assessed the feasibility of incorporating patient-reported outcome (PRO) measures as an adjunct to traditional endpoints. METHODS: Sorafenib, continuous oral twice daily dosing, was administered with irinotecan, orally, once daily days 1-5, repeated every 21 days (NCT01518413). Based on tolerability, escalation of sorafenib followed by escalation of irinotecan was planned. Three patients were initially enrolled at each dose level. Sorafenib and irinotecan PK analyses were performed during cycle 1. PRO measurements were collected during cycles 1 and 2. RESULTS: Fifteen patients were evaluable. Two of three patients at dose level 2 experienced dose-limiting toxicity (DLT), grade 3 diarrhea, and grade 3 hyponatremia. Therefore, dose level 1 was expanded to 12 patients and two patients had DLT, grade 4 thrombocytopenia, grade 3 elevated lipase. Nine of 15 (60%) patients had a best response of stable disease with four patients receiving ≥6 cycles. CONCLUSIONS: The recommended dose for pediatric patients was sorafenib 150 mg/m2 /dose twice daily with irinotecan 70 mg/m2 /dose daily × 5 days every 21 days. This oral outpatient regimen was well tolerated and resulted in prolonged disease stabilization. There were no significant alterations in the PK profile of either agent when administered in combination. Patients were willing and able to report their subjective experiences with this regimen.


Asunto(s)
Irinotecán , Neoplasias , Sorafenib , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Niño , Humanos , Irinotecán/efectos adversos , Irinotecán/uso terapéutico , Dosis Máxima Tolerada , Recurrencia Local de Neoplasia , Neoplasias/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/efectos adversos , Inhibidores de Proteínas Quinasas/uso terapéutico , Sorafenib/efectos adversos , Sorafenib/uso terapéutico
14.
Neuro Oncol ; 22(11): 1647-1657, 2020 11 26.
Artículo en Inglés | MEDLINE | ID: mdl-32506137

RESUMEN

BACKGROUND: This study describes imaging features of diffuse intrinsic pontine glioma (DIPG) and correlates with overall survival (OS) and histone mutation status in the International DIPG Registry (IDIPGR). METHODS: Four hundred cases submitted to the IDIPGR with a local diagnosis of DIPG and baseline MRI were evaluated by consensus review of 2 neuroradiologists; 43 cases were excluded (inadequate imaging or alternative diagnoses). Agreement between reviewers, association with histone status, and univariable and multivariable analyses relative to OS were assessed. RESULTS: On univariable analysis imaging features significantly associated with worse OS included: extrapontine extension, larger size, enhancement, necrosis, diffusion restriction, and distant disease. On central review, 9.5% of patients were considered not to have DIPG. There was moderate mean agreement of MRI features between reviewers. On multivariable analysis, chemotherapy, age, and distant disease were predictors of OS. There was no difference in OS between wild-type and H3 mutated cases. The only imaging feature associated with histone status was the presence of ill-defined signal infiltrating pontine fibers. CONCLUSIONS: Baseline imaging features are assessed in the IDIPGR. There was a 9.5% discordance in DIPG diagnosis between local and central review, demonstrating need for central imaging confirmation for prospective trials. Although several imaging features were significantly associated with OS (univariable), only age and distant disease were significant on multivariable analyses. There was limited association of imaging features with histone mutation status, although numbers are small and evaluation exploratory.


Asunto(s)
Neoplasias del Tronco Encefálico , Glioma Pontino Intrínseco Difuso , Neoplasias del Tronco Encefálico/diagnóstico por imagen , Neoplasias del Tronco Encefálico/genética , Humanos , Imagen por Resonancia Magnética , Estudios Prospectivos , Sistema de Registros
15.
Neuropsychology ; 34(3): 350-358, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-31999166

RESUMEN

OBJECTIVE: The etiology of pediatric brain tumor survivor (PBTSs) social difficulties is not well understood. A model of social competence for youth with brain disorder and evidence from youth with autism spectrum disorder (ASD) suggests that diminished social attention may underlie social deficits in PBTSs. This study used eye tracking technology to compare visual social attention in PBTSs, youth with ASD, and typically developing (TD) youth. METHODS: Participants included 90 age-, gender-, and IQ-matched youth (N = 30 per group). PBTSs were at least 5 years from diagnosis and 2 years from the completion of tumor-directed therapy. Participants' eye gaze patterns were recorded while watching an established social play paradigm that presented videos of children engaging in either interactive or parallel play. Group differences in proportional gaze duration toward social versus nonsocial areas of interest were compared. Medical correlates of social attention in PBTSs were evaluated. RESULTS: Groups significantly differed in gaze preference across conditions, with PBTSs looking less at social areas of interest than TD youth and in a manner comparable to youth with ASD. Among PBTSs, multimodal tumor-directed therapy was associated with reduced gaze preference for faces. CONCLUSIONS: This study provides the first evidence of disrupted social attention in PBTSs, with parallels to the social attention deficits observed in ASD. Findings offer a new way to conceptualize the social difficulties of PBTSs and could guide interventions aimed at improving PBTS social adjustment by increasing visual attention to socially relevant information during social interactions. (PsycINFO Database Record (c) 2020 APA, all rights reserved).


Asunto(s)
Atención , Neoplasias Encefálicas/psicología , Supervivientes de Cáncer/psicología , Movimientos Oculares , Desempeño Psicomotor , Percepción Social , Adolescente , Trastorno del Espectro Autista/psicología , Niño , Cognición , Función Ejecutiva , Femenino , Fijación Ocular , Humanos , Relaciones Interpersonales , Masculino
16.
J Neurooncol ; 143(2): 305-312, 2019 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-30982198

RESUMEN

PURPOSE: Survivors of pediatric brain tumors often have neurodevelopmental late effects, such as inattention. Symptoms may mirror those of attention-deficit/hyperactivity disorder (ADHD), which affects ~ 5-8% of the general population. This retrospective study of survivors followed at a large tertiary care center examined the prevalence of a clinical diagnosis of ADHD, and risk factors associated with ADHD diagnosis and ADHD-related medication use. METHODS: A retrospective chart review of brain tumor survivors (n = 528), diagnosed between 2000 and 2015, who were at least 6 years old and 2 years from the end of tumor-directed therapy or from diagnosis, if no interventions were received. Clinical and demographic data were extracted from the medical record. RESULTS: Survivors were 55.7% male with mean age 8.15 ± 4.4 (0.0-16.0) years at brain tumor diagnosis. The most common diagnoses were low-grade glioma, medulloblastoma, and craniopharyngioma, with 52.5% of tumors supratentorial. Of the survivors, 81.3% received surgery, 40.0% radiation therapy, and 36.6% chemotherapy. Sixty-nine survivors (13.1%) had ADHD diagnoses, 105 (19.9%) had symptoms of ADHD without diagnoses, and 64 (12.1%) had ADHD medication use. ADHD diagnosis was associated with younger age at tumor diagnosis (p = 0.05) and supratentorial tumor location (p = 0.001). ADHD diagnosis was not associated with gender, tumor type, or treatment type. CONCLUSIONS: Survivors of brain tumors are at increased risk of ADHD and related symptoms. The greatest increase in risk occurs for survivors with diagnoses at younger ages and supratentorial tumors. Additional research is warranted, as select survivors may benefit from behavioral or pharmacologic ADHD treatments to optimize functioning.


Asunto(s)
Trastorno por Déficit de Atención con Hiperactividad/diagnóstico , Neoplasias Encefálicas/complicaciones , Sobrevivientes/estadística & datos numéricos , Adolescente , Adulto , Trastorno por Déficit de Atención con Hiperactividad/etiología , Niño , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Masculino , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia , Adulto Joven
19.
Int J Radiat Oncol Biol Phys ; 95(3): 991-998, 2016 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-27302514

RESUMEN

PURPOSE: Clinically effective measurement of cognitive toxicity from photon radiation therapy (XRT) should be accurate, sensitive, and specific. This pilot study tested translational findings on phasic changes in children's memory systems that are sensitive and insensitive to toxic XRT effects to identify a possible neuroplastic effect. METHODS AND MATERIALS: Memory processes were prospectively tested before XRT and at 3 later time points up to 2 years in 35 children with mixed primary brain tumors who had not experienced recurrence. Memory processes were verbal-semantic, visual-semantic, and visual-perceptual, including accuracy, speed to recall, encoding, retrieval, and recognition. The mixed-effects model included time (to estimate slope), covariates (age, tumor locus, XRT field, and medications) as fixed effects, and individual random intercepts. A sensitivity analysis examined the influence of XRT dose to the hippocampi on memory. RESULTS: Retrieval from long-term verbal-semantic memory declined 2 months after completing XRT, as seen in adults, and was lowest at 1 year, which was delayed in comparison with adults. Double dissociation from visual-perceptual memory at baseline and 2 months was found, consistent with adults. Recovery was demonstrated 2 years after XRT. Patterns were unchanged when dose to hippocampus was included in the model. CONCLUSIONS: Verbal and semantic long-term retrieval is specifically sensitive to XRT-related cognitive dysfunction, without effect on visual-perceptual memory. Children reached nadir in XRT-sensitive memory 1 year after XRT and recovered by 2 years, which is later than that observed in adults. The protracted period of post-XRT injury may represent the maturation of the human hippocampus and white matter into late adolescence.


Asunto(s)
Neoplasias Encefálicas/radioterapia , Disfunción Cognitiva/etiología , Disfunción Cognitiva/fisiopatología , Irradiación Craneana/efectos adversos , Plasticidad Neuronal/efectos de la radiación , Traumatismos por Radiación/fisiopatología , Encéfalo/fisiopatología , Encéfalo/efectos de la radiación , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/fisiopatología , Niño , Disfunción Cognitiva/diagnóstico , Irradiación Craneana/métodos , Femenino , Humanos , Estudios Longitudinales , Masculino , Proyectos Piloto , Traumatismos por Radiación/etiología , Dosificación Radioterapéutica , Recuperación de la Función/efectos de la radiación , Resultado del Tratamiento
20.
Pediatr Blood Cancer ; 63(1): 21-6, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26235452

RESUMEN

BACKGROUND: The high prevalence of carboplatin hypersensitivity reactions (HSR) significantly affects the treatment of pediatric patients with low-grade glioma (LGG). Rechallenging patients is an option that must balance the risks of repeat allergic reaction to the benefits of retaining an effective anti-tumor regimen. PROCEDURE: We performed a retrospective review of children with LGG treated with carboplatin and vincristine between October 2000 and April 2013, who had a documented HSR to carboplatin. Patients were re-exposed to carboplatin using either precautionary measures (prolonged infusion time and premedication with H1 antagonists, H2 antagonists, and corticosteroids), a desensitization protocol, or both. RESULTS: We report the results of our institutional experience of carboplatin re-exposure using both premedication with a prolonged infusion time and a desensitization protocol. Overall, 40 of 55 (73%) patients were successfully rechallenged with carboplatin, including 19 of 25 (76%) patients who underwent desensitization. CONCLUSION: Our results demonstrate re-exposure to be a safe alternative to abandoning carboplatin for patients with a hypersensitivity reaction. We propose a clinical algorithm for treatment.


Asunto(s)
Antineoplásicos/efectos adversos , Carboplatino/efectos adversos , Neoplasias del Sistema Nervioso Central/tratamiento farmacológico , Hipersensibilidad a las Drogas/terapia , Glioma/tratamiento farmacológico , Adolescente , Corticoesteroides/administración & dosificación , Algoritmos , Antineoplásicos/administración & dosificación , Antineoplásicos Fitogénicos/administración & dosificación , Carboplatino/administración & dosificación , Niño , Preescolar , Desensibilización Psicológica , Femenino , Antagonistas de los Receptores Histamínicos H1/administración & dosificación , Antagonistas de los Receptores H2 de la Histamina/administración & dosificación , Humanos , Lactante , Masculino , Clasificación del Tumor , Estudios Retrospectivos , Resultado del Tratamiento , Vincristina/administración & dosificación
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